Featured Research

from universities, journals, and other organizations

Fruit fly's pruning protein could be key to treating brain injury

Date:

February 27, 2014

Source:

Duke University

Summary:

A protein that controls the metamorphosis of the common fruit fly could someday play a role in reversing brain injuries. Cysteine proteinase-1 in the fly directs both the early development and regrowth of dendrites that relay information from neuron to neuron. Researchers are hopeful the mammalian equivalent of this molecule might be used to help regrow dendrites after injury.

Related Articles

This protein directs both the early development and regrowth of the tiny branches that relay information from neuron to neuron. Known as dendrites, these thin structures that resemble tree branches are responsible for receiving electrical impulses that flash throughout the body.

Incorrect dendrite development or injury has been linked to neurodevelopmental or psychiatric diseases in humans, such as autism, schizophrenia and fragile X syndrome.

Under normal circumstances, neural communication is easy, much like neighbors talking over a fence. But if a neuron is injured or malformed, they frequently don't have the proper dendrites needed to be functional.

"One of the major problems with the nervous system is that it doesn't regenerate very well after injury," said Chay Kuo, M.D., Ph.D., the George W. Brumley assistant professor of cell biology, neurobiology and pediatrics. "Neurons don't multiply, so when they're injured, there's a loss of function. We'd like to know how to get it back."

While prompting such regrowth in the human brain isn't currently possible, dendrite regeneration and arborization -- the branching out of dendrites from the body of the neuron -- are a necessary part of the fruit fly Drosophila's life cycle. In the larval (or worm) state, the fly's nervous system is attuned to what the smooth-skinned worm needs: finding food, locomotion and avoiding attack. As an adult with bristle-covered skin however, the nervous system must be wired for flying, finding mates and laying eggs.

Until now, researchers haven't understood how Drosophila sensory neurons are able to create two separate dendrite branching patterns that successfully serve different kinds of sensory environments, said Kuo, who is also a faculty member with the Duke Institute for Brain Sciences (DIBS). His team set out to find the genetic mechanism that makes it possible. This research, funded by the Alfred P. Sloan Foundation and the George & Jean Brumley, Jr. Endowment, will appear online in the Feb. 27 issue of Cell Reports.

The answer lies in the insect's metamorphosis from larvae to adult. During this transition, Drosophila lose the neurons they won't need for adult life. The remaining sensory neurons sever their dendrites and grow a completely different set. The regeneration process, which is controlled by the hormone ecdysone, is much like pruning a tree in spring to make room for new growth, Kuo said.

To find out how the drosophila sensory neurons accomplish this change, Kuo's team tagged abdominal sensory neurons with green fluorescent protein (GFP) and followed them through metamorphosis to see if their dendrite branching changed. The dendrite design and architecture was, in fact, different in the adult stage.

A test carried out by former graduate student Gray Lyons revealed Cysteine proteinase-1 (Cp1) is responsible for regulating the regeneration of neuron dendrites and innervating the adult sensory field. Kuo's team demonstrated that without Cp1, Drosophila sensory dendrites cannot regenerate after pruning.

Existing literature also pointed Kuo's team to a parallel between the drosophila nervous system and mammals.

"We investigated whether it was possible that Cp1, during metamorphosis, shuttles from the cytoplasm into the nucleus to cleave a transcription factor required for dendrite development, and makes it a new transcription factor for regeneration," Kuo said. "And, that turned out to be true."

The mammalian version of Cp1 is a protein known to be associated with cancer progression and other diseases called lysosomal protein capthesin-L (Ctsl). During the cell cycle, Ctsl can target a transcription factor -- a protein that binds specific DNA sequences -- called Cut-like 1 (Cux1) that plays a role in gene expression. Ctsl pursues Cux1 inside the nucleus and cleaves it, creating a smaller protein with different transcriptional properties than the original one.

"I feel this discovery is amazing because the major transcription factor involved in how fly sensory neurons grow dendrites in the first place is Cut, and Cut-like 1 is its mammalian homologue," Kuo said. "[Lyons'] initial idea looking into mammalian conservation for answers panned out big. It was serendipity."

By tagging Cut during Drosophila metamorphosis, Kuo's team observed the protein's binding pattern within the nucleus. Before dendrite pruning, Cut binds in big blobs. After the pruning, however, Cut binding is diffused, giving it an opportunity, Kuo said, to bind to different genes during the two dendrite growth phases.

The team translated this finding back to Cp1, discovering that it goes into the neuron nucleus to cleave Cut, making a new transcription factor required for dendrite regeneration after developmental pruning.

This research could also potentially impact how science and healthcare think about and treat brain injuries, Kuo said. Currently, damaged neurons that have lost their dendrites are unable to properly communicate with their neighbors, rendering them nonfunctional. The problem could be reversed, he said, by helping neurons modify their original developmental program and regrow new dendrites.

"If we can influence this environmental control that changes the development program, it's possible that we could get neurons to integrate and function better after injury," he said.

Story Source:

The above story is based on materials provided by Duke University. Note: Materials may be edited for content and length.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015  New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015  Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015  No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015  Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015  Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015  Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015  Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015  Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015  Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015)  After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015)  Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015)  A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

June 11, 2014  How neurons are created and integrate with each other is one of biology’s greatest riddles. Now, a researcher unravels a part of the mystery by describing a mechanism that explains novel aspects of ... full story

Jan. 9, 2014  A brand-new pathway for neuron repair has been discovered that could have implications for faster and improved healing after nerve damage. The research demonstrates, for the first time, that ... full story

June 5, 2013  Researchers have evidence that a single gene controls both halves of nerve cells, and their research demonstrates the need to consider that design in the development of new treatments for ... full story

Nov. 12, 2010  Researchers have improved the fruit fly as model for studying the connections between brain cells. The researchers developed a specific marker for a part of the fly's nerve cell which had ... full story

May 21, 2010  Researchers describe a laboratory test that allows scientists to evaluate large numbers of fruit fly genes for a possible role in the formation of plaque-like protein aggregates within cells. Those ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.